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Background:
The pathogenesis of gastric cancer (GC) involves environmental and genetic factors. Recently, two genome-wide association studies found that phospholipase C epsilon 1 (PLCE1) polymorphisms might be related to GC risk, and several studies further validated this finding. However, these studies yielded inconsistent results.
Methods:
A c...
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Gastric cancer (GC) is a common cause of cancer-related death. The etiology and pathogenesis of GC remain unclear, with genetic and epigenetic factors playing an important role. Previous studies investigated the association of GC with many genetic variants in and promoter hypermethylation of E-cadherin gene (CDH1), with conflicting results reported...
Citations
... We confirmed the significance of the two SNPs previously reported, rs3765524 and rs2274223, and revealed another SNP in PLCE1, rs3781264, through genotyping and logistic regression in this case-control study was associated with the GC risk. Abnet et al. (2010) firstly used GWAS to identify those variants of PLCE1 had a significant correlation with GC in the Chinese Han population Until now, an increasing number of studies have identified a shared susceptibility locus in PLCE1 such as rs2274223 A > G and rs3765524 C > T for gastrointestinal cancer (Abnet et al., 2010;Umar et al., 2013;Cui et al., 2014b;Liu et al., 2014;Malik et al., 2014;Mocellin et al., 2015;He et al., 2016;Gu et al., 2018;Li et al., 2018;Liang et al., 2019;Xie et al., 2020), and the most reported SNP of PLCE1 was the former, but the conclusions lack consistency. A meta-analysis showed that PLCE1 rs2274223 polymorphism resulted in susceptibility to esophageal and GC in Asians (Umar et al., 2013). ...
Background
Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 (PLCE1) single-nucleotide polymorphisms (SNPs) and GC susceptibility, but its relationship with GC prognosis lacked exploration, and the specific mechanisms were not elaborated fully yet. This study aimed to further explore the possible mechanism of the association between PLCE1 polymorphisms and GC.
Materials and Methods
A case-control study, including 588 GC patients and 703 healthy controls among the Chinese Han population, was performed to investigate the association between SNPs of PLCE1 and GC risk by logistic regression in multiple genetic models. The prognostic value of PLCE1 in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of PLCE1, various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations.
Results
Rs3765524 C > T, rs2274223 A > G and rs3781264 T > C in PLCE1 were associated with the increased risk of GC. The overall survival and progression-free survival of patients with high expression of PLCE1 were significantly lower than those with low expression [HR (95% CI) = 1.38 (1.1–1.63), P < 0.01; HR (95% CI) = 1.4 (1.07–1.84), P = 0.01]. Bioinformatic analysis revealed that PLCE1 was associated with protein phosphorylation and played a crucial role in the calcium signal pathway. Two important functional domains, catalytic binding pocket and calcium ion binding pocket, were found by homology modeling of PLCE1 protein; rs3765524 polymorphism could change the efficiency of the former, and rs2274223 polymorphism affected the activity of the latter, which may together play a potentially significant role in the tumorigenesis and prognosis of GC.
Conclusion
Patients with high expression of PLCE1 had a poor prognosis in GC, and SNPs in PLCE1 were associated with GC risk, which might be related to the changes in spatial structure of the protein, especially the variation of the efficiency of PLCE1 in the calcium signal pathway.
... Some studies have reported AG, GG or AG+GG genotypes are more susceptible to different cancers, particularly for esophageal/gastric cancer or esophageal squamous cell carcinoma compared to AA genotype 20,21 . In a meta-analysis study on 13676 patients with gastric cancer, it has been concluded that there is a significant relationship between PLCE1 rs2274223 polymorphisms and the incidence and increased risk of gastric cancer 22 . Cui et al. investigated the relationship between four functional SNPs in PLCE1 gene (including rs12263737, rs2274223, rs11187842 and rs753724) and the risk of esophagus cancer in 222 Chinese cases and 326 controls 23 . ...
Background: Phospholipase C epsilon 1 (PLCE1) gene harbors different single nucleotide polymorphisms (SNPs), which can be correlated with the risk of different types of cancers. In this case-control study, the relationship between rs2274223 (A>G), a single nucleotide polymorphism in phospholipase C epsilon gene (PLCE1), and gastric cancer was evaluated among Iranian patients.
Materials and Methods: The PLCE1 rs2274223 polymorphism was genotyped in 60 patients with gastric cancer and 69 control subjects using polymerase chain reaction and restriction fragment length polymorphisms (PCR-RFLP) methods. Clinical and pathologic parameters such as tumor characteristics and disease stage were also recorded.
Results: There were 48 (80%) male patients and 45 (65.5%) healthy male individuals (p=0.077). About 34 (56.6%) patients were smokers. A family history of gastric cancer was found in 21 (35%) cases. GG genotype was observed among 15% of patients and 8.7% of normals, respectively. There was no significant difference between the AA and AG genotypes. Also, there were no significant correlations between AA, AG or GG genotypes and the risk of gastric cancer, gender, tumor size, tumor stage, grade, as well as tumor location and metastasis.
Conclusion: The PLCE1 rs2274223 polymorphism was not correlated with gastric cancer in Iranian population. However, a further comprehensive study with largersample sizes is needed.
... Wang et al. performed a genome-wide association in Chinese populations with ESCC and found that PLCE1 was a susceptibility gene for ESCC and PLCE1 might regulate cell growth, differentiation, apoptosis, and angiogenesis [5]. Several studies have also shown that PLCE1 plays a critical role in a variety of human cancers, such as skin cancer [6], gastric cancer [7][8][9], bladder cancer [10], gallbladder cancer [11], head and neck cancer [12], and large intestinal cancer [13,14]. It also has been confirmed that germline genetic variants in the susceptibility locus of the PLCE1 gene (10q23) were related to the risk of ESCC and has been recognized as a novel susceptibility marker for ESCC [15,16]. ...
Phospholipase C epsilon 1 (PLCE1) has been recognized as a novel susceptibility marker for esophageal squamous cell carcinoma (ESCC). The purpose of our study is to investigate its effect on the regulation of miRNA expression so as to translating the data into a novel strategy in control of ESCC. In this study, PLCE1 siRNA and vector-only plasmid were stably transfected into Eca109 and EC9706 cells and then subjected to miRNA array analysis, and quantitative real-time PCR was applied to validate miRNA array data. Then bioinformatic analyses, such as GO and pathway software, were conducted to obtain data on these differentially expressed miRNAs-targeted genes (DEGs) and clarify their function and pathway. The results showed that 36 miRNAs were found to be differentially expressed in PLCE1 siRNA-transfected cells compared with the control cells. In particular, 28 miRNAs were upregulated while 8 miRNAs were downregulated. Gene Ontology analysis showed that the function of the DEGs included cell cycle arrest, cell–matrix adhesion, apoptosis, etc. After this, the major pathways associated with the DEGs were regulation of actin cytoskeleton, TGF-beta signaling pathway, Notch signaling pathway and so on. Taken together, these results showed that the knockdown of PLCE1 may play a vital role in the control of ESCC. Further investigation will reveal and verify the function and pathway of the DEGs for the development of novel treatment strategy for the better control of ESCC.
... on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million cancer‑related deaths occurred in 2012 worldwide.[3]Although many risk factors contribute to the development of cancer, including genetic variants,[4,5]obesity,[6]smoking,[7]poor diet,[8]physical inactivity,[9]and reproductive factors[10](including lower parity and higher age at first birth), such risk factors account for only a small proportion of cancer cases. Thus, other unknown risk factors still need to be identified. ...
Background: Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case–control studies.
Methods: PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle–Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score.
Results: A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35–2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of
... Both 2010 GWAS studies mentioned previously found that PLCE1 variants were risk factors for GC (Abnet et al., 2010;Wang et al., 2010) and many subsequent studies have confirmed these findings. To date, nine meta-analyses have been conducted on the PCLE gene polymorphisms (Duan et al., 2014;Xue et al., 2015;Cui et al., 2014;Liu et al., 2014;Umar et al., 2013;Hao et al., 2013;Zhang et al., 2013a;Mai et al., 2013;Zhang et al., 2013b). The largest meta-analysis grouped 11 studies that included both Asians and Caucasians, and reported that the polymorphic G allele (rs2274223) was significantly associated with an increased risk of GC; however, the evidence was specifically stronger among Asians. ...
... However, the results of this meta-analysis are in disagreement with other studies. Some authors have found a significant association between this SNP and cardia tumours (Duan et al., 2014;Liu et al., 2014;Hao et al., 2013;Mai et al., 2013), whereas one study showed no significant association with either cardia and non-cardia tumours, despite a confirmed risk association for overall gastric tumours. This controversial result may be due to the eligible studies and statistical power in this meta-analysis (Zhang et al., 2013a). ...
... Sun et al., 2015) Korean(Saeki et al., 2011) Caucasian(Song et al., 2014) ↓GC(Carvalho et al., 1997;Silva et al., 2001;Xu et al., 2009;Jia et al., 2010;Sun et al., 2015; Duan et al.Sun et al., 2015) Indian(Zhang et al., 2011(Zhang et al., , 2013bLi et al., 2013) Cardia(Mocellin et al., 2015;Abnet et al., 2010;Wang et al., 2010;Duan et al., 2014;Liu et al., 2014;Hao et al., 2013;Mai et al., 2013) GC(Sun et al., 2014;Abnet et al., 2010;Zhang et al., 2011;Song et al., 2014;Duan et al., 2014;Liu et al., 2014;Umar et al., 2013;Hao et al., 2013;Zhang et al., 2013a;Li et al., 2013;Wang et al., 2012c;Malik et al. ...
Cancer is a multifactorial disease that involves many molecular alterations. Gastric cancer (GC) is the third leading cause of cancer death worldwide. GC is a highly heterogeneous disease with different molecular and genetics features. Therefore, this review focuses on an overview of the genetic aspects of gastric cancer by highlighting the important impact and role of deletions and/or duplications of chromosomal segments, genomic variants, H. pylori infection and interleukin variants, as found in gene expression and newly proposed molecular classification studies. The challenge is to better understand the mechanisms and different pathways that lead to the development and progression of GC.
... We also confirmed that the heterozygote of PLCE1 rs2274223 increase susceptibility to HPV infection in Kazakh patients with esophageal carcinoma [13]. Studies also revealed that PLCE1 plays crucial roles in several tumor types, such as gastric [14][15][16], bladder [17], head and neck [18], gallbladder [19], and colorectal cancer [20,21]. However, research on PLCE1 expression in ESCC provides contradicting findings. ...
Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3'UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.
Objective:
In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms (SNPs) on candidate genes and gastric cancer (GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.
Methods:
We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability (FPRP) test.
Results:
Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1 (rs1760944), DNMT1 (rs16999593), ERCC5 (rs751402), GSTT1 (null/presence), MDM2 (rs2278744), PPARG (rs1801282), TLR4 (rs4986790), IL-17F (rs763780), and CASP8 (rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.
Conclusions:
Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk; however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.
Recently, the roles of interleukin‐2 (IL‐2), IL‐4, IL‐6 and IL‐8 gene polymorphisms in gastric cancer (GC) have been extensively studied, with conflicting results. Therefore, we conducted the present meta‐analyses to better elucidate the roles of interleukin gene polymorphisms in GC. Eligible articles were searched in PubMed, Medline, Embase, Web of Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential association between interleukin gene polymorphisms and the risk of GC. A total of 63 case‐control studies was finally included in our analyses. Significant associations with the risk of GC were detected for the IL‐6 rs1800796 and IL‐8 rs4073 polymorphisms in overall analyses. Further subgroup analyses based on ethnicities of participants revealed that the IL‐4 rs2243250, IL‐6 rs1800796 and IL‐8 rs4073 polymorphisms were significantly associated with the risk of GC in Asians. Moreover, IL‐8 rs4073 polymorphism was also significantly associated with the risk of GC in Africans. In conclusion, our findings suggested that IL‐4 rs2243250, IL‐6 rs1800796 and IL‐8 rs4073 polymorphisms may serve as genetic biomarkers of GC.
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Hollow fiber cell fishing, based on HepG-2, SKOV-3, and ACHN cancer cells, and hollow fiber liquid/solid microextraction with HPLC were developed and introduced for researching the anti-cancer activity of Rhizoma Curcumae Longae, Radix Curcumae, and Rhizoma Curcumae. The structures of curcumin, demethoxycurcumin and bisdemethoxycurcumin screened were identified and their contents were determined. The compound target fishing factors and cell apoptosis rates under the effect of the three medicines were determined. The binding sites (cell membrane and cell organelle) and binding target (phospholipase C) on the cell were researched. Hollow fiber liquid/solid-phase microextraction mechanism was analyzed and expounded. Before the application, cell seeding time, growth state and survival rate, compound non-specific binding, positive and negative controls, repeatability in hollow fiber cell fishing with high-performance liquid chromatography; extraction solvent, sample pH, salt concentration, agitation speed, extraction time, temperature and sample volume in hollow fiber liquid/solid-phase microextraction with high-performance liquid chromatography were investigated. The results demonstrated that the proposed strategy is a simple and quick method to identify bioactive compounds at the cellular level as well as determine their contents (particularly trace levels of the bioactive compounds), analyze multi-compound and multi-target entirety effects, and elucidate the efficacious material base in traditional medicine. This article is protected by copyright. All rights reserved.
